1. Field of the Invention
The present invention relates to novel crystalline free base forms of a dimethylphenyl compound, which compound is expected to be useful as a therapeutic agent for treating pulmonary disorders. This invention also relates to pharmaceutical compositions containing or prepared from such crystalline forms; processes and intermediates useful for preparing such crystalline forms; and methods of using such crystalline forms to, for example, treat a pulmonary disorder.
2. State of the Art
Commonly-assigned U.S. application Ser. No. 11/789,300, filed on even date herewith now U.S. Pat. No. 7,524,965 B2) and U.S. Provisional Application No. 60/794,702, filed Apr. 25, 2006, (the disclosures of which are incorporated herein by reference in their entirety) disclose novel dialkylphenyl compounds that are useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease (COPD) and asthma. In particular, the compound, biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]-piperidin-4-yl ester is specifically disclosed in this application as possessing both muscarinic antagonist and β2 adrenergic receptor agonist activity. The chemical structure of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester is represented by formula I:

Therapeutic agents useful for treating pulmonary disorders are advantageously administered directly into the respiratory tract by inhalation. In this regard, several types of pharmaceutical inhalation devices have been developed for administering therapeutic agents by inhalation including dry powder inhalers (DPI), metered-dose inhalers (MDI) and nebulizer inhalers. When preparing pharmaceutical compositions and formulations for use in such devices, it is highly desirable to have a crystalline form of the therapeutic agent that is neither hygroscopic nor deliquescent and which has a relatively high melting point (i.e. greater than about 130° C.) thereby allowing the material to be micronized without significant decomposition or loss of crystallinity.
No crystalline forms of the compound of formula I have been disclosed previously. Accordingly, a need exists for a stable, non-deliquescent crystalline form of the compound of formula I that has an acceptable level of hygroscopicity and a relatively high melting point.